LAUSR

November 13, 2018 2295 Half of patients with heart failure have preserved ejection fraction (HFpEF), and few effective treatments are available.1 Elevation in left ventricular (LV) filling pressures plays a dominant role in the pathophysiology of HFpEF, contributing to symptoms of dyspnea, impaired exercise capacity, pulmonary hypertension, and increased morbidity and mortality.1–3 Although left ventricular diastolic dysfunction is the dominant cause of elevated LV filling pressures in HFpEF, a substantial component of the increase in filling pressure is not related to alterations in viscoelastic muscle properties but is rather mediated by external restraining effects attributable to the contact pressure exerted by the pericardium and right heart.4,5 We have recently shown in animal preparations that surgical resection of the pericardium improves effective LV diastolic compliance, even as muscle properties remain unchanged, because these external constraining effects are eliminated.5 This led us to hypothesize that a similar benefit on LV diastolic reserve might be attainable in humans with surgical pericardiotomy. To test this hypothesis, we compared the change in LV filling pressures with volume loading with pericardium intact and again after opening the pericardium for surgical access in patients with risk factors for HFpEF who were referred for cardiac surgery for aortic valve or coronary artery disease. Subjects undergoing clinically-indicated cardiac surgery were prospectively enrolled. Hemodynamics were measured invasively under general anesthesia with the sternum open and pericardium intact at baseline and then immediately after acute increase in cardiac preload, achieved by leg elevation with or without 250 mL saline bolus. The pericardium was then opened, and hemodynamics were measured again at baseline and following the same volume load as performed when the pericardium was intact. The prespecified primary end point was the change in LV filling pressure (pulmonary capillary wedge pressure [PCWP]) in response to volume loading before and after opening the pericardium. Written informed consent was obtained by all patients before evaluation. The study was approved by the Mayo Clinic Institutional Review Board and the trial was registered (NCT03073668). Nineteen subjects (32% women) undergoing aortic valve replacement (42%), coronary artery bypass grafting (26%), or both (32%) were enrolled. Subjects displayed multiple risk factors for HFpEF: mean age was 71±10 years, mean body mass index was 32.5±5.3 kg/m2; hypertension was present in 79%, coronary disease in 74%, atrial fibrillation in 21%, and diabetes mellitus in 47%. LV systolic function was preserved (ejection fraction 59±10%) but diastolic dysfunction was highly prevalent (E/e’ 14±5, left atrial volume index 36±13 mL/m2) and plasma NTproBNP levels were elevated (594±333 pg/mL). Baseline PCWP under general anesthesia with the sternum open and pericardium intact was mildly elevated (16±5 mm Hg). Volume loading with combined leg raise and saline infusion increased PCWP to 25±5 mm Hg, an increase of +9±3 mm Hg compared with baseline (P<0.0001 by paired t test; Figure, panel A). Leg raise alone Barry A. Borlaug, MD Hartzell V. Schaff, MD Alberto Pochettino, MD Dawn M. Pedrotty, MD, PhD Samuel J. Asirvatham, MD Martin D. Abel, MD Rickey E. Carter, PhD William J. Mauermann, MD